Stroke is the third leading cause of death and a major contributor to disability, particularly in the elderly. Prevention os stroke through risk factor identification and modification continues to be the key mechanism to reducing the incidence of stroke and the burden of resultant disability. The major objective of this proposal is to extend the study of precursors, manifestations and outcome of stroke in the original Framingham Study cohor and to expand the population to include the Framingham Offspring cohort, wh are now predominantly middle-aged and entered into the Framingham Study twenty years after the original cohort. The specific aims of this study ar to relate measured risk factors to the development of symptomatic cerebrovascular disease, to identify secular trends in incidence, prevalenc and case-fatality from stroke, and to document outcome following stroke including neurologic deficits, functional disability and institutionalization, stroke recurrence and other atherosclerotic comorbidity. In particular, the role of stroke as a precursor of dementia and depression will be examined and correlated with MRI imaging. Over the next five years we will identify all new incident cases in the Framingham Study, evaluate and follow each new event over a two year period and analyze current and previously collected risk factor data on stroke cases to the general population sample as a means to determine independent contributors to stroke. In addition to characterization and verification o stroke by type, obtaining MR-scans in cases and matched control will enable us to explore the relationship of stroke and MR-defined clinically unapparent cerebral lesions to the decline in cognitive function and the development of dementia and of depression. There will be definitive analysis of the relation of repeated measurements of cognitive function, stroke risk factors and incidence of stroke to the development of dementia and depression. Lastly, examination of noninvasive carotid and cardiac functional measures will be related to subsequent occurrence, type and severity of stroke.